Objective To observe the pathological changes of hippocampus and myelin in rats with frontal cereberal ischemia and reperfusion after treated with methylcobalamine and to discuss the mechanism of the cerebral protective effect of methylcobalamine.Methods Cerebral ischemia and reperfusion models were made by clamping bilateral carotid arteries.Forty-five male Wistar rats were randomly allocated to sham-operation group,ischemia-reperfusion group and methylcobalamine group(n=15).1,2,4 weeks after reperfusion the rats in each group were divided into three groups(n=5).The pathological changes of hippocampus and myelin were observed by using light microscope,HE staining,LFB staining and electron microscope.Results The pyramidal neurons in hippocampus in ischemia and reperfusion groups expressed putrescence and myelin necrosis or demyelination at 1st week,and the histomorphological changes at 4th week were significant than that at 2nd week.The followings were observed in electron microscope: dimness,partly solubilization and collapsablity in myelin.The pyramidal neurons in hippocampus of therapy groups were similar to normal one and myelin expressed compaction and shipshape.The changes were more obvious at 4th week.Conclusion Methylcobalamine can obviously decrease the ischemia lesion of hippocampus and myelin and protect the brain function.